The immediate objective of this investigation is to perfect methods to measure the amount of lung tissue (Vt) and lung water in contact with the airways. These methods will be based principally upon the simultaneous differential disappearance rates of insoluble gases, and CO2 labelled with oxygen of mass 18 during rebreathing. These methods will be non-invasive and permit frequent repetition. Measurements will be performed in humans in the healthy state, in acute respiratory distress, and with minor modifications in the unconscious state. Animals will be studied via an endotracheal tube. Factors such as lung volume, dead space, breathing frequency, and cardiac output will be varied in order to determine the most accurate way to use these methods. A variety of analytical systems will be evaluated to develop the simplest and most reliable technique for performing the measurements. Limitations of these new methods for measuring Vt will be examined by making comparisons with established methods such as ratio of wet to dry weight of the lung, determinations of the pulmonary extravascular water volume (PEV) by the double indicator dilution method, and microscopic assessment of abnormalities of lung tissue. Once the accuracy and limitations of these methods are established, normal values for humans and dogs will be established. Measurements of lung tissue and lung water volume will be made in various disease states suspected of increasing or decreasing these volumes. Clinical applications will include detection, assessment, and observation of response to therapy in the following conditions: diseases with elevated pulmonary vascular pressures, cardiac and non-cardiac pulmonary edema, "fluid overload syndrome", and interstitial disease such as sarcoidosis and pulmonary fibrosis. Physiological mechanisms involved in the development of hypoxic pulmonary edema and central nervous system pulmonary edema will be studied.